title: PRRT2 mutations: exploring the phenotypical boundaries.
abstract: BACKGROUND
  Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene have been identified in patients with benign (familial) infantile convulsions (B(F)IC), infantile convulsions with choreoathetosis (ICCA) and paroxysmal dyskinesias (PDs). However it remains unknown whether PRRT2 mutations are causal in other epilepsy syndromes. After we discovered a PRRT2 mutation in a large family with ICCA containing one individual with febrile seizures (FS) and one individual with West syndrome, we analysed PRRT2 in a heterogeneous cohort of patients with different types of infantile epilepsy.
  
  
  METHODS
  We screened a cohort of 460 patients with B(F)IC or ICCA, fever related seizures or infantile epileptic encephalopathies. All patients were tested for point mutations using direct sequencing.
  
  
  RESULTS
  We identified heterozygous mutations in 16 individuals: 10 familial and 6 sporadic cases. All patients were diagnosed with B(F)IC, ICCA or PD. We were not able to detect mutations in any of the other epilepsy syndromes. Several mutation carriers had learning disabilities and/or impaired fine motor skills later in life.
  
  
  CONCLUSIONS
  PRRT2 mutations do not seem to be involved in the aetiology of FS or infantile epileptic encephalopathies. Therefore B(F)IC, ICCA and PD remain the core phenotypes associated with PRRT2 mutations. The presence of learning disabilities or neuropsychiatric problems in several mutation carriers calls for additional clinical studies addressing this developmental aspect in more detail.
authors.affiliation: Neurogenetics Group, Department of Molecular Genetics, VIB, , Antwerp, Belgium.
authors.forename: Tania
authors.initials: T
authors.lastname: Djémié
authors.forename: Sarah
authors.initials: S
authors.lastname: Weckhuysen
authors.forename: Philip
authors.initials: P
authors.lastname: Holmgren
authors.forename: Katia
authors.initials: K
authors.lastname: Hardies
authors.forename: Tine
authors.initials: T
authors.lastname: Van Dyck
authors.forename: Rik
authors.initials: R
authors.lastname: Hendrickx
authors.forename: An-Sofie
authors.initials: AS
authors.lastname: Schoonjans
authors.forename: Wim
authors.initials: W
authors.lastname: Van Paesschen
authors.forename: Anna C
authors.initials: AC
authors.lastname: Jansen
authors.forename: Linda
authors.initials: L
authors.lastname: De Meirleir
authors.forename: Laila Abdel Moteleb
authors.initials: LA
authors.lastname: Selim
authors.forename: Marian Y
authors.initials: MY
authors.lastname: Girgis
authors.forename: Gunnar
authors.initials: G
authors.lastname: Buyse
authors.forename: Lieven
authors.initials: L
authors.lastname: Lagae
authors.forename: Katrien
authors.initials: K
authors.lastname: Smets
authors.forename: Iris
authors.initials: I
authors.lastname: Smouts
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
authors.forename: Vic
authors.initials: V
authors.lastname: Van den Bergh
authors.forename: Thierry
authors.initials: T
authors.lastname: Grisar
authors.forename: Ilan
authors.initials: I
authors.lastname: Blatt
authors.forename: Zamir
authors.initials: Z
authors.lastname: Shorer
authors.forename: Filip
authors.initials: F
authors.lastname: Roelens
authors.forename: Zaid
authors.initials: Z
authors.lastname: Afawi
authors.forename: Ingo
authors.initials: I
authors.lastname: Helbig
authors.forename: Berten
authors.initials: B
authors.lastname: Ceulemans
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Arvid
authors.initials: A
authors.lastname: Suls
mesh_terms: D004827:Epilepsy / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007859:Learning Disabilities / Q000150:complications / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D019957:Motor Skills Disorders / Q000150:complications / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human
keywords: CLINICAL NEUROLOGY; EPILEPSY; GENETICS; NEUROGENETICS